Clozapine Protects Patients With Tx-resistant Schizophrenia Against Self-harm

Clozapine might lower risk of self-harm for patients with treatment-resistant schizophrenia.

Clozapine has demonstrated a protective effect against self-harm in patients with treatment-resistant schizophrenia compared with other antipsychotics, according to a study in American Journal of Psychiatry.

Theresa Whimberley, PhD, of Aarhus University in Denmark, and colleagues conducted a population-based cohort study comprised of 2370 individuals who had been diagnosed with treatment-resistant schizophrenia after January 1, 1996.

“The aim of the present study was to evaluate rates of all-cause (and cause-specific) mortality and self-harm in association with clozapine treatment and alternative antipsychotic treatment strategies among individuals with schizophrenia meeting criteria for treatment resistance,” Dr Whimberley said.

The study followed patients through one of the following: death, the first episode of self-harm, emigration, or June 1, 2013. At follow-up, 1372 individuals (58%) in the study initiated clozapine treatment. Nonclozapine antipsychotic treatment was associated with an elevated risk of self-harm (hazard ratio [HR]: 1.36) compared with clozapine after adjusting for confounding factors. Non-use of clozapine treatment was associated with an elevated rate of all-cause mortality (HR: 1.88) compared with clozapine treatment.

Rates of all-cause mortality were highest after clozapine discontinuation, especially within the first year following discontinuation compared with rates during clozapine treatment. When compared with no antipsychotic treatment, clozapine use was associated with a lower overall mortality rate.

“The results of the present study indicate that clozapine use is associated with a decreased mortality rate,” the researchers said. “This was, however, only significant when clozapine treatment was compared with periods of no antipsychotic treatment, a situation probably largely explained by an excess mortality rate observed after clozapine discontinuation.”

“It remains unclear whether the protective effect of clozapine on self-harm in treatment-resistant schizophrenia could be partly explained by a potentially harmful effect of alternative treatment strategies with other antipsychotics or confounding by indication,” they added. “Moreover, the extent to which the observed excess mortality rate after clozapine discontinuation is caused by side effects from recent clozapine exposure, unobserved factors, or clozapine discontinuation remains to be investigated.”

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Wimberley T, MacCabe JH, Laursen TM, et al. Mortality and self-harm in association with clozapine in treatment-resistant schizophrenia [published online July 28, 2017]. Am J Psychiatry. doi:10.1176/appi.ajp.2017.16091097.